| 2013 |
Y26 phosphorylation of PGAM1 enhances its activation by releasing an inhibitory glutamate (E19) that blocks the active site, thereby stabilizing cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. Crystal structure of H11-phosphorylated PGAM1 revealed that phospho-H11 activates the enzyme at least in part by promoting substrate 3-phosphoglycerate binding. |
Crystal structure determination, active-site mutagenesis, in vitro enzymatic assays, mass spectrometry |
Nature communications |
High |
23653202
|
| 2024 |
PKM2 moonlights as a histidine kinase, using phosphoenolpyruvate (PEP) as the phosphate donor to phosphorylate PGAM1 at H11, which is essential for PGAM1 activity. Monomeric and dimeric but not tetrameric PKM2 efficiently phosphorylate PGAM1. Src-catalyzed PGAM1 Y119 phosphorylation (downstream of EGF signaling) is a prerequisite for PKM2 binding and subsequent H11 phosphorylation. |
In vitro kinase assay, Co-IP, cell-permeable phosphopeptide competition, site-directed mutagenesis, metabolic flux analysis, xenograft tumor growth assay |
The EMBO journal |
High |
38750259
|
| 2022 |
PGAM1 is succinylated at K99 by HAT1 (a writer), and this succinylation enhances PGAM1 enzymatic activity. Aspirin reduces NF-κB p65-dependent HAT1 expression, thereby decreasing PGAM1 K99 succinylation and suppressing glycolysis. PGAM1-K99R mutant failed to rescue aspirin-induced inhibition of enzymatic activity. |
Site-directed mutagenesis (K99R), Co-IP, RNA-seq, in vitro succinylation assay, metabolic flux measurement (ECAR), in vivo xenograft |
Acta pharmacologica Sinica |
Medium |
35835856
|
| 2024 |
KAT2A interacts with PGAM1 and promotes succinylation of PGAM1 at K161, enhancing its activity and glycolysis in hepatocellular carcinoma. AS-IV treatment reduces KAT2A expression and consequently decreases PGAM1 K161 succinylation. |
Co-immunoprecipitation, immunofluorescence, site-directed mutagenesis, xenograft tumor model, metabolic assays |
BMC cancer |
Medium |
38835015
|
| 2022 |
USP46 directly interacts with PGAM1 and enhances its protein stability by reducing ubiquitination, thereby promoting glycolysis and malignant growth in triple-negative breast cancer. |
Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown functional assays, metabolic flux measurement |
Cell biology international |
Medium |
36335636
|
| 2025 |
SEC61G directly antagonizes the E3 ubiquitin ligase UBE3C to prevent UBE3C-mediated proteasomal degradation of PGAM1, thereby stabilizing PGAM1 protein levels and enhancing glycolysis to support NSCLC brain metastatic colonization. |
Co-immunoprecipitation, ubiquitination assay, transcriptomics, in vivo brain-metastasis mouse model, pharmacological inhibition |
International journal of biological sciences |
Medium |
39990664
|
| 2025 |
SYVN1, an E3 ubiquitin ligase, mediates K48-linked polyubiquitination and proteasomal degradation of PGAM1 in hepatocellular carcinoma; dihydrotanshinone I induces this pathway to suppress glycolysis. |
Proteasomal degradation assays, ubiquitination assays, in vitro enzymatic activity measurement, orthotopic and subcutaneous xenograft models |
Phytotherapy research : PTR |
Medium |
40640077
|
| 2025 |
UBE2S interacts with PGAM1 and OTUB2; through OTUB2-mediated K48-linked deubiquitylation, UBE2S prevents PGAM1 degradation, stabilizes PGAM1 protein levels, promotes DNA repair, and reduces glioblastoma cell sensitivity to temozolomide. |
IP-mass spectrometry, co-immunoprecipitation, ubiquitination assay, knockdown functional assays, in vivo GBM mouse model |
International journal of biological macromolecules |
Medium |
39904430
|
| 2021 |
PGAM1 overexpression in gliomas promotes resistance to irradiation and chemotherapy by sequestering the phosphatase WIP1 in the cytoplasm, thereby preventing inactivation of the ATM DNA damage response signaling pathway. |
Genetic inhibition (knockdown), cellular fractionation/localization assay, DNA damage response pathway analysis |
Molecular & cellular oncology |
Medium |
33860077
|
| 2020 |
T cell-specific deletion of Pgam1 in mice attenuates both CD8 and CD4 T cell-dependent immune responses and reduces helper T cell-dependent inflammation. Glycolysis (mediated by PGAM1) augments mTORC1 and TCR signaling, and glutamine acts as a metabolic hub linking glycolysis, mTORC1, and TCR activation to T cell proliferation and differentiation. |
T cell-specific conditional knockout mice, metabolomics (Soga), in vivo immune challenge assays, signaling pathway analysis |
Communications biology |
High |
32709928
|
| 2020 |
PGAM1 directly interacts with TGF-β and mediates NF-κB, p38, JNK, and TGF-β signaling pathway activation in cardiomyocytes, contributing to inflammation, apoptosis, and fibrosis during myocardial ischemia-reperfusion injury. Cardiac-specific PGAM1 knockout mice are protected from these injuries. |
Cardiac-specific knockout mice, co-immunoprecipitation, in vitro OGDR model, signaling pathway analysis, histology |
Biochemical and biophysical research communications |
Medium |
33168191
|
| 2018 |
The S1P/S1PR3 axis inhibits YAP phosphorylation, promotes nuclear YAP translocation, and facilitates formation of a YAP–c-MYC protein complex that enhances transcription of PGAM1, thereby promoting aerobic glycolysis in osteosarcoma cells. |
Co-immunoprecipitation (YAP–c-MYC complex), chromatin immunoprecipitation (YAP/c-MYC binding to PGAM1 promoter), luciferase reporter assay, RNA-seq, metabolic flux analysis (XF96), xenograft model |
EBioMedicine |
High |
30587459
|
| 2018 |
NUDT7 acts upstream of PGAM1 in chondrocyte glycolysis; knockout of NUDT7 upregulates PGAM1, and overexpression of PGAM1 alone recapitulates lipid accumulation, IL-1β upregulation, and apoptotic cell death seen in Nudt7-/- mice. Co-introduction of NUDT7 reverses PGAM1-induced negative effects on cartilage homeostasis. |
Nudt7-/- mouse model, genome-wide analysis, gain/loss-of-function in chondrocytes, epistasis rescue experiment |
Nature communications |
High |
30143643
|
| 2015 |
Knockdown of PGAM1 in bladder cancer cells upregulates substrate 3-phosphoglycerate and downregulates product 2-phosphoglycerate, consequently inhibiting aerobic glycolysis and the oxidative pentose phosphate pathway (PPP), which are essential for cancer cell proliferation. |
RNAi knockdown, metabolite measurement (3-PG/2-PG), in vivo xenograft |
Journal of proteomics |
Medium |
26655504
|
| 2023 |
Exosomal PGAM1 from prostate cancer cells is transferred to HUVECs, where it binds to γ-actin (ACTG1) via GST-pulldown and Co-IP, promoting podosome formation and neovascular sprouting, thereby facilitating angiogenesis and metastasis. |
GST pulldown, co-immunoprecipitation, in vitro angiogenesis assay, gelatin degradation assay, in vivo tail-vein metastasis mouse model |
Cell death & disease |
Medium |
37542027
|
| 2022 |
PGAM1 negatively regulates argininosuccinate synthase 1 (ASS1) expression through the cAMP/AMPK/CEBPB signaling axis in breast cancer; PGAM1 knockdown upregulates ASS1, which suppresses malignant behavior. |
RNA sequencing, knockdown/rescue functional assays, signaling pathway analysis, in vivo xenograft, immunohistochemistry |
Molecular oncology |
Medium |
35674458
|
| 2023 |
PGAM1 inhibition promotes hepatocellular carcinoma ferroptosis by downregulating Lipocalin 2 (LCN2) via energy stress and ROS-dependent AKT inhibition, which also downregulates PD-L1, synergizing with anti-PD-1 immunotherapy. |
In vitro and in vivo loss-of-function (siRNA/allosteric inhibitor KH3), PDX models, metabolic assays, mechanistic pathway analysis |
Advanced science |
Medium |
37505495
|
| 2025 |
AUF1, an RNA-binding protein phosphorylated and inactivated by MST1 kinase during senescence, promotes decay of PGAM1 mRNA. Loss of AUF1 activity stabilizes PGAM1 mRNA, accelerating glycolysis-driven pyruvate production and cellular senescence. |
mRNA decay assay, RNA immunoprecipitation, overexpression/knockdown in human diploid fibroblasts, phosphorylation analysis |
Aging |
Medium |
40711448
|
| 2026 |
STAT3 directly binds to the PGAM1 promoter to transcriptionally upregulate PGAM1 expression in acute pancreatitis; 17β-estradiol suppresses this axis to reduce inflammatory injury. |
ChIP assay, dual-luciferase reporter assay, JASPAR bioinformatics prediction, ELISA, in vivo AP mouse model |
Immunobiology |
Medium |
42044555
|
| 2023 |
RFX6 directly binds to the promoter region of PGAM1 and upregulates its expression, increasing glycolysis and promoting hepatocellular carcinoma development. |
Chromatin immunoprecipitation, metabolome profiling, functional assays in vitro and in vivo |
Clinical and translational medicine |
Medium |
38093528
|
| 2026 |
PGAM1 promotes pathological oligomerization of VDAC1 in cardiomyocytes exposed to doxorubicin, disrupting mitochondrial quality control and triggering mitochondrial DNA leakage into the cytosol, which activates the cGAS-STING innate immune pathway and culminates in cardiomyocyte ferroptosis. |
Cardiomyocyte-specific PGAM1 knockout mice, co-immunoprecipitation, immunofluorescence, Western blot, pharmacological inhibitors, echocardiography |
Free radical biology & medicine |
Medium |
41651300
|
| 2026 |
METTL14 promotes PGAM1 mRNA m6A methylation, enhancing PGAM1 mRNA stability and glycolysis in non-small cell lung cancer; METTL14 is itself stabilized by lactylation in a feedback loop. |
m6A-RIP, RNA stability assay, knockdown/rescue, metabolic flux measurement, IP for lactylation |
Immunological investigations |
Medium |
42023502
|
| 2025 |
NAT10 promotes ac4C modification of PGAM1 mRNA, enhancing its stability and consequently increasing glycolysis and cell stemness in ovarian cancer. |
RNA immunoprecipitation (ac4C-specific RIP), dot blot, dual-luciferase reporter, knockdown/rescue, sphere formation assay |
Scientific reports |
Medium |
41198892
|
| 1982 |
The PGAM1 (PGAMA) locus was mapped to human chromosome 10q26.1 (or 10q25.3) by gene-dosage studies in patients with chromosomal imbalances. |
Gene dosage analysis in trisomic/monosomic patients |
Annales de genetique |
Medium |
6282177
|
| 2024 |
PGAM1 Y119 tyrosine phosphorylation (by Src downstream of EGF signaling) was identified by parallel phosphoproteomics and metabolomics as a functionally significant modification; phosphomutant and phosphomimetic PGAM1 isoforms confirmed the metabolic consequence of this site. |
Parallel phosphoproteomics and polar metabolomics in MCF10A cells, CRISPRi depletion with doxycycline-inducible re-expression of wild-type/mutant isoforms, EGF stimulation/EGFR inhibitor treatment |
bioRxivpreprint |
Medium |
bio_10.1101_2024.05.14.594136
|